Some tumors appear to escape immune rejection by suppressing a host's immune response. We have come one step closer to understanding one possible mechanism of immunosuppression utilized by a murine tumor cell line, Carcinoma D2, with the demonstration that this cell line releases soluble factors which antagonize the action of at least one lymphokine, T-cell Growth Factor (now Interleukin-2, IL-2). Increasing concentration of IL-2 overcomes the suppressive activity in an IL-2-dependent suppressive activity through the responding lymphocytes. The working hypothesis is that there is IL-2 antagonist interaction rendering IL-2 incapable of delivering a mitogenic signal. IL-2 plays a critical role in the development of cytotoxic T lymphocytes. Tumor-produced antagonists of this lymphokine would result in immunosuppression and would be a survival advantage to cells bearing tumor antigens. The soluble immunosuppressants fall into at least three groups varying greatly in molecular weight. One group is greater than 150,000 daltons, one about 100,000 and a third group is less than 1,000 daltons. The antagonists are resistant to heat and trypsin. Based upon this information this proposal has six specific aims: (1) to biochemically characterize the CaD2-produced suppressive factors; (2) to better define the mechanism of suppressive factor-lymphokine antagonism; (3) to assess the possiblity that exogenous IL-2, administered in vivo, can cause tumor regression or slow tumor growth; (4) to detect suppressive factors in the serum of tumor-bearing mice; (5) to determine whether the suppressive factors antagonize other lymphokine-dependent lymphocyte proliferation responses; and (6) to determine whether other murine tumors of epithelial origin produce lymphokine antagonists. Understanding possible mechanisms of tumor immunosuppression is important to future strategies that may be employed for tumor treatment and management. The particular model of tumor immunosuppression, tumor-lymphokine antagonism, which I propose to examine would appear to be an efficient and effective means for tumors to suppress the immune system and thus result in a tumor survival advantage. (HF)